Some heterocyclic compounds, e.g., piperidines, possess pharmaceutical activity. It has been reported that their pharmaceutical activity, as well as safety, varies based on the stereochemical configurations of the substituents on the piperidine ring. See, e.g., Pharmacia, 1989, 25(4), 311-336. Thus, effective synthesis of piperidines with high stereo-selectivity is of great importance.
Methods for preparing cis/trans mixtures of piperidines, e.g., piperidine-3-carboxamide, are well known in the field. See, e.g., DeNinno et al., Bioorganic and Medicinal Letters, 2011, 21, 3095-3098; and Gancia et al., WO 2015/091584. Yet, conventional methods produce either non-stereo selective isomers or mainly cis-isomers.
There is a need to develop a new method for preparing trans-isomeric piperidines.